High resolution solid state NMR will be used to investigate the structure and dynamics of peptides and proteins. The research can be divided into three categories. Protein Dynamics: We are labelling the small protein BPTI (from E. Coli.) with 2H, 13C and 15N amino acids, and will study its spectra to determine the rates and mechanism of the side chain dynamics. The studies will include examinations of single crystals to perform assignments, and of mutant BPTIs to elucidate the role of site specific changes on dynamics. Although BPTI has been intensively studied in solution, there is actually very little information available on its amino acid side chain dynamics. This study should lead to a comprehensive picture of the dynamic structure of BPTI. In addition, will investigate the dynamics of small molecules and solvent bound to proteins. The plan is to correlate the motion of the two, as a function of temperature and with biochemical properties. Structure of Enzyme/Inhibitor Complexes: The second area of research is enzyme/inhibitor structure. The focus is large (approximately 40 dK) proteins or problems which are not accessible with solution NMR techniques, and involves low temperature, magic angle spinning (MAS) chemical shift or dipolar shift spectra. In alpha-lytic protease we will measure N-H distances in His-57 and between His and Ser-195 of the catalytic triad. In thermolysin/phosphonamidate inhibitor complexes we will measure PN bond lengths and the degree of portonation of the N to understand the structure of these transition state analogue inhibitors. Alanine racemase is inhibited by alanine borate, and with IIB NMR we plan to determine the structure of the EI complex. Finally, D- ala-D-ala ligase is inhibited by aminoalkylphosphinate, presumably via formation of a phosphophospinate ester. We plan to investigate the structure of this EI complex with 31P MAS NMR. Solid State Correlation Spectroscopy: Recently, we have developed a new solid state NMR experiment referred to as rotational resonance (R@) which permits determination of distances up to 5-6 angstroms in solids. This techniques is potentially quite useful for determining protein structures, but at the moment it is in an embryonic stage of development. We are plan to extend the method in several ways; for example, by developing two quantum filtering and rotating frame versions of the technique. Finally, we plana to continue development of heteronuclear versions of R2 and of heteronuclear chemical shift correlation spectroscopy.